# Fibrosis Severity in MASLD Determines the Predictive Value of Lp-PLA2 for Carotid Atherosclerosis in Type 2 Diabetes: A Cross-Sectional Study

## TL;DR

This study shows that high Lp-PLA2 levels are linked to carotid atherosclerosis in type 2 diabetes patients with advanced liver fibrosis, but not in those without it.

## Contribution

The study identifies a specific Lp-PLA2 threshold for predicting cardiovascular risk in T2DM patients with MASLD and advanced fibrosis.

## Key findings

- Lp-PLA2 activity was higher in MASLD patients compared to non-MASLD individuals.
- Lp-PLA2 levels above 570 U/L were a risk factor for carotid atherosclerosis in patients with advanced liver fibrosis.
- No association was found between Lp-PLA2 and the degree of liver steatosis.

## Abstract

Background: Elevated Lp-PLA2 activity, a marker of inflammation and oxidative stress, is linked to increased cardiovascular disease (CVD) risk in type 2 diabetes mellitus (T2DM). Given that high Lp-PLA2 activity is a hallmark of metabolic-dysfunction-associated steatotic liver disease (MASLD), we aimed to investigate whether it contributes additional CVD risks when MASLD coexists with T2DM. Methods: This study included 1095 patients with T2DM, consecutively enrolled at the First Affiliated Hospital, Sun Yat-sen University, between June 2020 and November 2022. Liver steatosis and stiffness were assessed via abdominal ultrasound/CT and fibrosis-4 (FIB-4) scores, respectively. Carotid atherosclerosis (CAS) was defined as the presence of intima-media thickening or carotid plaque and was evaluated using high-resolution B-mode ultrasonography. Results: Among 674 MASLD patients, higher levels of Lp-PLA2 activity were observed compared to those in 421 non-MASLD individuals (573 ± 164 U/L vs. 540 ± 170 U/L, p = 0.002), while no association was found between steatosis degree and Lp-PLA2. Lp-PLA2 levels exceeding a threshold of 570 U/L were identified as a risk factor for CAS, with each one standard deviation increase in Lp-PLA2 corresponding to an odds ratio of 2.67 (95% confidence interval: 1.31–5.42, p = 0.007), while a similar association was not observed in patients with normal FIB-4 levels. Conclusions: Elevated Lp-PLA2 activity is associated with MASLD and insulin resistance in T2DM, while Lp-PLA2 was not related to the degree of liver steatosis. A threshold of 570 U/L is associated with CAS risk, specifically in those with concurrent advanced liver fibrosis, highlighting the potential role of Lp-PLA2 in cardiovascular risk stratification in this subset but within the limitations of a cross-sectional study.